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Biomedical subjects

J Howard

Publications and source records attributed to J Howard.

At least 37 records · Page 2Linked to original sources
PubMed2001

Can bacterial interference prevent infection?

The concept that one bacterial species can interfere with the ability of another to colonize and infect the host has at its foundation the prerequisite that bacteria must attach to biological surfaces to cause infection. Although this is an over-simplification of pathogenesis, it has led to studies aimed at creating vaccines that block adhesion events. Arguably, the use of commensal bacteria (also referred to as "normal flora", "indigenous" or "autochthonous" microorganisms) to inhibit pathogens has even greater potential than vaccine use, because these bacteria are natural competitors of pathogens and their action does not require host immune stimulation. Exogenous application of commensal organisms (probiotics) has been shown to reduce the risk of infections in the gut, urogenital tract and wound sites. To manipulate and optimize these effects, further studies are required to understand cell signaling amongst commensals and pathogens within biofilms adherent to host tissues. The potential for new therapeutic regimens using probiotics is significant and worthy of further study.

Antibiosis↗
PubMed2001

Aspartame effect in sickle cell anemia.

OBJECTIVE: To examine the in vitro and in vivo attributes of aspartame and to determine its efficacy for treating sickle cell anemia. RATIONALE: Aspartame (l-aspartyl-l-phenylalanine methyl ester) binds with 2 human Bence Jones proteins. The proteins (Mcg and Sea) showed phenylalanine penetrating into hydrophobic binding sites. This aspartame property suggested a potential to interfere with sickle hemoglobin fibril formation. METHODS: For the in vitro studies, blood from 20 subjects monitored for sickle cell anemia was collected in heparinized tubes. Specimens were divided in thirds and aspartame was added to 2 tubes to yield a 1 mg/mL or 2 mg/mL concentration. Sickled cells that were present after a drop from each aliquot was added to a fresh 2% metabisulfite solution were counted 3 times. For the in vivo studies, 23 subjects from the Sickle Cell Clinic (University of Oklahoma Health Sciences Center, Oklahoma City, Okla) consented to participate in a randomized single-dose administration of 1.5, 3.0, or 6 mg/kg aspartame. Heparinized blood was obtained at 0, 30, 60, 120, 240, 480, and 1440 minutes after aspartame administration. Specimens were counted in a blinded manner by means of the technique used for the in vitro method, but a photomicrograph of 1 field from each triplicate count was made. The pictures were marked and were computer counted. RESULTS: For the in vitro studies, sickled cells decreased from 28% to < 14% when 1 mg/mL aspartame was added and decreased further with 2 mg/mL. For the in vivo studies, a decreased number of sickled cells in homozygous blood (HbSS) were observed after oral administration of aspartame. Sickling was inhibited by 6 mg/kg aspartame for at least 6 hours in 15 subjects with HbSS anemia. CONCLUSIONS: Further evaluations of the efficacy of aspartame for sickle crisis and crisis prevention appears to be warranted.

Administration, Oral↗
PubMed2001

Lipoinjection augmentation of the soft palate for velopharyngeal stress incompetence.

OBJECTIVES/HYPOTHESIS: Velopharyngeal stress incompetence in professional musicians is an uncommon but potentially career-ending problem. Pharyngeal flaps, V-Y palatal pushback procedures, Teflon or collagen injection of the posterior pharyngeal wall, and speech therapy have all been used to address this problem. The ideal procedure for this subset of patients with velopharyngeal incompetence (VPI) with high-pressure, mild VPI would be one that combines low morbidity and an expedient recovery for the busy musician. We describe an approach of endoscopically assisted autologous lipoinjection of the soft palate. STUDY DESIGN: A retrospective review of our experience treating high-pressure stress VPI in two professional musicians. METHODS: Literature review and retrospective chart review. RESULTS: Two musicians underwent autologous lipoinjection of the soft palate for stress VPI. Patients resumed full play within 2 weeks of the operation with no serious complications. There has been no recurrence of the VPI after 18 and 12 months of follow-up, respectively. CONCLUSIONS: Velopharyngeal stress incompetence in musicians is an uncommon disorder. Velopharyngeal incompetence in these patients may not present as in a typical manner with hypernasality but may go undiagnosed for years mistakenly rationalized as a declining performance ability rather than a curable structural problem. The performance demands of professional musicians necessitate a timely solution to their VPI. More precise and limited contouring of palatal bulk can be achieved through the lipoinjection technique than compared with traditional palatal V-Y pushback or a standard pharyngeal flap. Lipoinjection of the palate can be performed as an outpatient procedure with only minor discomfort and an expedient recovery for the career musician.

Adipose Tissue↗
PubMed2001

Acute erythremic myelosis (true erythroleukaemia): a variant of AML FAB-M6.

AIMS: Classic erythroleukaemia (acute myeloid leukaemia M6, or M6 AML) is defined as an excess of myeloblasts in an erythroid predominant background. Leukaemia variants in which the primitive blast cells are demonstrably erythroid are extremely rare and poorly characterised. Variably referred to as "true erythroleukaemia" or "acute erythremic myelosis", they are often included within the M6 AML category even though they do not meet strict criteria for this type of AML. METHODS: Two cases of acute erythroid neoplasia are presented with clinical, morphological, immunophenotypic, and cytogenetic analysis. RESULTS: Both patients presented with profound anaemia, one in a setting of long standing myelodysplasia. Bone marrow examination revealed a predominant population of highly dysplastic erythroid cells in both cases. In one case, the liver was infiltrated by neoplastic erythroid cells. Both patients died within four months of diagnosis. CONCLUSIONS: This report illustrates that cases of acute leukaemia occur in which the dominant neoplastic cell is a primitive erythroid cell without an accompanying increase in myeloblasts. This does not preclude the neoplastic clone originating in a multipotent haemopoietic stem cell, as suggested by cases arising in patients with myelodysplasia. Acute erythremic myelosis should be recognised as a distinct variant of M6 AML.

Adult↗
PubMed2001

Nuisance flies around a landfill: patterns of abundance and distribution.

Some members of the public living near landfills perceive the sites as a source of nuisance flies and their associated diseases. Both these factors contribute to frequent complaints to Environmental Health Officers about landfill operations. Fly monitoring using sticky targets was done at a working landfill site in the West Midlands in order to identify the key species of flies present at the site, and to establish whether these flies were similar to those occurring in the surrounding area. Targets were positioned in concentric rings, radiating away from the working face into the surrounding residential area. The abundance of the flies, both in and around the landfill site was monitored over a 6-week period commencing 16 August 1999. The key families of flies present on targets on the landfill site were Muscidae, principally Musca domestica L. (common house fly), Calliphoridae, (primarily 'blue' and 'green' bottles), and Sarcophagidae (flesh flies). In contrast, the families of flies found on targets immediately outside the working landfill site and in the nearby surrounding area, were largely vegetation-feeding or parasitic flies, together with other non-fly insects. The overall abundance of all flies increased significantly during the monitoring period.

Animals↗
PubMed2001

Taxotere resistance in SUIT Taxotere resistance in pancreatic carcinoma cell line SUIT 2 and its sublines.

AIM: To investigate the specific mechanisms of intrinsic and acquired resistance to taxotere (TXT) in pancreatic adenocarcinoma (PAC). METHODS: MTT assay was used to detect the sensitivity of PAC cell line SUIT-2 and its sublines (S-007, S-013, S-020, S-028 and TXT selected SUIT-2 cell line, S2/TXT) to TXT. Mdr1 (P-gp), multidrug resistance associated protein (MRP), lung resistance protein (LRP) and beta-tubulin isotype gene expressions were detected by RT-PCR. The functionality of P-gp and MRP was tested using their specific blocker verapamil (Ver) and indomethacin (IMC), respectively. The transporter activity of P-gp was also confirmed by Rhodamine 123 accumulation assay. RESULTS: S-020 and S2/TXT were found to be significantly resistant to TXT(19 and 9.5-fold to their parental cell line SUIT-2, respectively). RT-PCR demonstrated strong expression of Mdr1 in these two cell lines, but weaker expression or no expression in other cells lines. MRP and LRP expressions were found in most of these cell lines. The TXT-resistance in S2-020 and S2/TXT could be reversed almost completely by Ver, but not by IMC. Flow cytometry showed that Ver increased the accumulation of Rhodamine-123 in these two cell lines. Compared with S-020 and SUIT-2, the levels of beta-tubulin isotype II, III expressions in S-2/TXT were increased remarkably. CONCLUSION: The both intrinsic and acquired TXT-related drug resistance in these PAC cell lines is mainly mediated by P-gp, but had no relationship to MRP and LRP expressions. The increases of beta-tubulin isotype II, III might be collateral changes that occur when the SUIT-2 cells are treated with TXT.

Antineoplastic Agents, Phytogenic↗
PubMed2001

Jonathon Howard.

Jonathon 'Joe' Howard (Fig. 1) is Group Leader and Director at the Max Planck Institute of Molecular Cell Biology and Genetics; he and his research group moved to Dresden, Germany, in July 2001. Howard received his PhD in neurobiology in 1983 from the Australian National University in Canberra. He did postdoctoral research there and also at the University of Bristol, UK, and at the University of California, San Francisco. In 1989, he joined the faculty at the University of Washington. His book "Mechanics of Motor Proteins and the Cytoskeleton" was published earlier this year. [interview by Mari N. Jensen]

Animals↗
PubMed2000

Epo regulates erythroid proliferation and differentiation through distinct signaling pathways: implication for erythropoiesis and Friend virus-induced erythroleukemia.

We have recently isolated the erythroleukemic cell line, HB60-5, that proliferates in the presence of erythropoietin (Epo) and stem cell factor (SCF), but undergoes terminal differentiation in the presence of Epo alone. Ectopic expression of the ets related transcription factor Fli-1 in these cells resulted in the establishment of the Epo-dependent cell line HB60-ED that proliferates in the presence of Epo. In this study, we utilized these two cell lines to examine the signal transduction pathways that are activated in response to Epo and SCF stimulation. We demonstrate that Epo, but not SCF, phosphorylates STAT-5 in both HB60-5 and HB60-ED cells. Interestingly, SCF activates the Shc/ras pathway in HB60-5 cells while Epo does not. However, both Epo and SCF are capable of activating the Shc/ras pathway in HB60ED cells. Furthermore, enforced expression of gp55 in HB60-5 cells by means of infection with the Spleen Focus Forming virus-P (SFFV-P), confers Epo independent growth, which is associated with the up-regulation of Fli-1. Activation of the Shc/ras pathway is readily detected in gp55 expressing cells in response to both Epo and SCF, and is associated with a block in STAT-5B tyrosine phosphorylation. These results suggest that STAT-5 activation, in the absence of Shc/ras activation, plays a role in erythroid differentiation. Moreover, Fli-1 is capable of switching Epo-induced differentiation to Epo-induced proliferation, suggesting that this ets factor regulated genes whose products modulate the Epo-Epo-R signal transduction pathway.

Adaptor Proteins, Signal Transducing↗
PubMed2000

Borato-1,2-diaminocyclohexane platinum (II), a novel anti-tumor drug.

Borato-1,2-diaminocyclohexane platinum (II) (BDP) was synthesized and compared to cisplatin (cisPt) as a potential anti-tumor drug. BDP and cisPt (0.2-20 microM) dose-dependently inhibited DNA synthesis in L1210 murine leukemia cells, DU-145 prostate cancer cells, A549 lung carcinoma cells, and MCF-7 breast cancer cells, as judged by measuring [(3)H]-thymidine incorporation. BDP and cisPt induced killing of L1210 murine cells by 97 and 78%, respectively. The LD(50) was 35 and 14 mg/kg for BDP and cisPt, respectively. Interestingly, while cisPt (at optimal dose) induced a 100% increase in life span (ILS) of BDF1 mice bearing L1210 tumor cells, BDP (at optimal dose) induced a 200% increase in ILS in the same tumor model. In conclusion, BDP is a novel platinum derivative compound that appears more effective in increasing the ILS than cisplatin against the leukemia tumor mouse model.

Animals↗
PubMed2000

Osmotic effects on feline spermatozoa from normospermic versus teratospermic donors.

Effects of osmolality stresses on the sperm of normospermic (>60% normal sperm/ejaculate) versus teratospermic (<40% normal sperm) domestic cats and the normospermic leopard cat and the teratospermic clouded leopard were studied. Spermatozoa were exposed to various anisotonic solutions in a single step or returned to near isotonic conditions in a single step after exposure to anisotonic solutions. The percentage of sperm motility was measured subjectively, and dual fluorescent stains were used to assess membrane integrity by flow cytometry. The percentage of sperm motility declined (P < 0.05) in domestic cat sperm exposed to osmolalities <200 and >450 mOsm. Spermatozoa from all felines underwent marked (P < 0.05) membrane disruption following a hypotonic stress, but sperm from teratospermic donors experienced greater (P < 0.05) membrane disruption in response to decreased osmolality. While feline spermatozoa appeared to be highly resistant to hypertonic (600, 1200, and 2400 mOsm) conditions, with >85% of the cells maintaining intact membranes, severe membrane disruption occurred when cells were returned to isotonicity in a single step. There was no difference (P > 0.05) between a 1- and 5-min exposure to various anisotonic solutions. Similarly, sperm from normospermic and teratospermic domestic cats responded identically after exposure to ionic or nonionic solute. Results demonstrate that: (1) spermatozoa from teratospermic males are more vulnerable to a hypotonic stress than sperm from normospermic counterparts; (2) in response to small deviations in osmolality, feline sperm experience a more rapid decline in motility than membrane integrity; and (3) an abrupt return to isotonicity after a hypertonic stress causes extensive sperm membrane damage regardless of ejaculate quality.

Animals↗
PubMed2000

Intrusive caregiving and quality of attachment in prenatally drug-exposed toddlers and their primary caregivers.

The relation between caregiver intrusiveness and the quality of attachment was tested among 51 prenatally drug-exposed toddlers and their primary caregivers. Biological mothers and kinship/foster caregivers neither differed as to caregiver intrusiveness nor as to their toddlers' attachment security and attachment organization. Insecure and disorganized/disoriented attachments were found to be more prevalent in this sample than in normal samples. In keeping with recent findings in non-drug-abusing samples (Isabella & Belsky, 1991; Lyons-Ruth, Repacholi, McLeod, & Silva, 1991), more caregivers of toddlers with avoidant or disorganized/disoriented attachments were found to be intrusive than caregivers of toddlers with secure or resistant attachments.

Adult↗
PubMed2000

The effects of tetanus toxin on the orbicularis oculi muscle.

PURPOSE: Tetanus toxin can cause localized neuromuscular weakness, but it also can produce systemic tetany. The action of tetanus toxin on the orbicularis muscle has not been studied in animals immunized to prevent systemic tetany. Our objective was to determine whether tetanus toxin could be used to treat orbicularis oculi muscle spasms. METHODS: We analyzed the clinical, electrophysiologic, and histopathologic effects of tetanus toxin injected into the orbicularis oculi muscle of rabbits with passive immunity to tetanus toxin. In six rabbits, the orbicularis oculi function in both eyes was assessed clinically, and the baseline orbicularis oculi muscle action potential was measured physiologically with electromyography (EMG). The rabbits then were immunized against tetanus toxin with tetanus immunoglobulin for immediate and definitive immunity. Tetanus toxin was injected into the left orbicularis oculi muscles, leaving the right eyes as controls. Ten days later, the rabbits were again assessed by clinical examination and with EMGs on both the injected side and the noninjected side. The animals were killed at 14 days, and the orbicularis muscle was removed from both sides. The injected and control tissues were examined microscopically for signs of neuromuscular denervation. RESULTS: All six rabbits showed weakness in eye closure on the side injected with tetanus toxin. In addition, four rabbits developed complete ear ptosis on the tetanus toxin injected side because of spread of the toxin to adjacent ear muscles. EMGs showed both a denervation of the orbicularis oculi muscle and a poor blink potential on the side injected with tetanus toxin. Histopathologic studies of the orbicularis oculi muscle injected with tetanus toxin showed angulation of both slow and fast types of muscle fibers compatible with neuromuscular denervation. CONCLUSIONS: Tetanus toxin can cause localized orbicularis oculi weakness, as documented clinically, physiologically, and microscopically, without producing systemic tetany in immunized rabbits. Tetanus toxin may have a potential application in the treatment of blepharospasm and hemifacial spasm.

Action Potentials↗
PubMed2000

Communicable disease and infection control: the surveillance contribution.

In its much-publicized report (2000) the National Audit Office (NAO) has emphasized the important part surveillance plays in determining infection rates and infection control in general. Community nurses may be forgiven for pointing out that this report concentrates on hospitals, however it strongly recommends that surveillance be extended out into the community. This is a sensible move as studies quoted in the NAO report indicate that 50-70% of surgical wound infection occur during the post-discharge period. The boundaries between acute and primary care are becoming ever more blurred; increasing numbers of susceptible patients are being managed in the community and the number of invasive procedures carried out is rising in line with government policy. Action to control infection extends beyond the narrow boundaries of health care to involve the whole population, and although the idea of extending the surveillance of healthcare related infection from hospital to community settings appears to be relatively new, the surveillance of infectious diseases that occur in the community is not. It is, in effect, a key proactive infection control activity which facilitates targeted and effective infection control measures. This article aims to define and explain surveillance as it relates to infection control and communicable disease control in the community by using examples from history, the current Meningitis C vaccination programme and the surveillance of hospital-acquired infection in the USA.

Communicable Disease Control↗
PubMed2000

Reliability, repeatability, and sensitivity of the modified shuttle test in adult cystic fibrosis.

STUDY OBJECTIVES: The purpose of this study was to investigate the test-retest reliability, repeatability, and sensitivity of the modified shuttle test (MST) in adult patients with cystic fibrosis (CF). DESIGN: : Prospective study. SETTING: Adult CF Unit, Belfast City Hospital. PATIENTS: : Adult patients with CF. INTERVENTIONS: Test-retest reliability-none; sensitivity-inpatient IV antibiotic therapy for an acute exacerbation of respiratory disease. MEASUREMENTS: The test-retest reliability and repeatability of the MST was assessed by comparing performance on two consecutive MSTs performed in 12 patients with CF and stable disease. The sensitivity of the MST was assessed by measuring the change in MST performance after 2 weeks of IV antibiotic therapy in 24 patients admitted to hospital with acute exacerbations of their respiratory disease. RESULTS: In the assessment of test-retest reliability and repeatability (n = 12), there was a significant and strong correlation between trials for distance completed (Pearson's r = 0. 99; p < 0.01), peak heart rate (Pearson's r = 0.99; p < 0.01), peak arterial oxygen saturation (SaO(2); Pearson's r = 0.99; p < 0.01), and peak Borg rating of perceived breathlessness (Pearson's r = 0. 99; p < 0.01). The coefficients of repeatability for these variables were small (coefficient of repeatability: distance completed, 4 shuttles; peak heart rate, 6 beats/min; peak SaO(2), 4%; and peak Borg rating of perceived breathlessness, 0.9). In the assessment of sensitivity (n = 24), the standardized response mean (SRM) for distance completed on MST (SRM = 1.18) was the SRMs for spirometric measures of lung function (FEV(1), SRM = 0.96; FEV(1) percent predicted, SRM = 0.88). CONCLUSIONS: This study demonstrates that the MST is a reliable, repeatable, and sensitive measure of exercise capacity in adult CF. The MST may be of value in determining prognosis, evaluation for lung transplantation, exercise prescription, and establishing the impact of new treatments on the disability associated with CF.

Adolescent↗
PubMed2000

Novel streptopyrroles from Streptomyces rimosus with bacterial protein histidine kinase inhibitory and antimicrobial activities.

A series of halogenated pyrrolo [2,1-b] [1,3] benzoxazines (1 approximately 9) was isolated from fermentations of an actinomycete strain X10/78/978 (NCIMB40808), identified as Streptomyces rimosus, during a microbial extract screening programme to identify inhibitors of bacterial histidine kinase. The structures of these compounds were elucidated by spectroscopic methods including the HMQC, HMBC and INADEQUATE NMR experiments. The structure of 1 was confirmed by X-ray crystallographic studies. Compounds 5 and 6 were produced in fermentations in the presence of NaBr and NaI respectively. The most abundant member of the series, streptopyrrole, 1, inhibited the nitrogen regulator II (NRII) histidine kinase from Escherichia coli with an IC50 of 20 microM and exhibited antimicrobial activity against a range of bacteria and fungi.

Anti-Bacterial Agents↗
PubMed2000

Stem cell factor inhibits erythroid differentiation by modulating the activity of G1-cyclin-dependent kinase complexes: a role for p27 in erythroid differentiation coupled G1 arrest.

Terminal erythroid differentiation is accompanied by decreased expression of c-Kit and decreased proliferation of erythroid progenitor cells. Using a newly established erythroleukemia cell line HB60-5, which proliferates in response to erythropoietin (Epo) and stem cell factor (SCF) and differentiates when stimulated with Epo alone, we characterized several events associated with the cell cycle during erythroid differentiation. Forty-eight h after SCF withdrawal and Epo stimulation, there was strong inhibition of cyclin-dependent kinase (cdk) 4 and cdk6 activities, associated with an increase in the binding of p27 and p15 to cdk6. A significant increase in the binding of p27 to cyclin E- and cyclin A-associated cdk2 correlated with the inhibition of these kinases. In addition, the expression of c-Myc and its downstream transcriptional target Cdc25A were found to be down-regulated during Epo-induced terminal differentiation of HB60-5 cells. The loss of Cdc25A was associated with an increase in the phosphotyrosylation of cyclin E-associated cdk2, which may contribute to cell cycle arrest during differentiation. Although overexpression of p27 in HB60-5 cells caused G1 arrest, it did not promote terminal erythroid differentiation. Thus, the cell cycle arrest that involves p27 is part of a broader molecular program during HB60-5 erythroid differentiation. Moreover, we suggest that SCF stimulation of erythroblasts, in addition to inhibiting erythroid differentiation, activates parallel or sequential signals responsible for maintaining cyclin/cdk activity.

Animals↗